The recent discovery and cloning of the BRCA1 gene (Miki 1994), which predisposes to breast and ovarian cancers, corroborates extensive genetic and epidemiologic data on familial patterns of inheritance and establishes a genetic contribution to their etiology. To estimate the distribution and characteristics of BRCA1 mutations in a population-based series of breast and ovarian cancer cases, the investigators propose to retrieve 1,355 paraffin-embedded breast tissue blocks from young black and white women diagnosed with breast cancer between 1980 and 1982 who were part of a large multi-center population-based case-control study. Tissue blocks from 250 women with ovarian cancer, who were part of the same parent study, have already been collected. For all cases, extensive risk factor and follow-up information have also been collected and computerized. The goals of this study are to: (1) explore the frequency, location, and type of germline BRCA1 mutations among a population-based sample of young black and white women with breast and/or ovarian cancer, with and without a family history of cancer; (2) describe the clinical features of genetic subtypes of breast or ovarian cancers diagnosed in black and white women who have specific germline mutations (or groups of mutations) of the BRCA1 gene; (3) determine risk factors for genetic subtypes of breast and/or ovarian cancer (as defined by mutations, or groups of mutations of the BRCA1 gene) among black and white women; and (4) evaluate the possibility of somatic mutations in a population-based study of women with breast or ovarian cancer. BRCA1 analyses of the paraffin-embedded tissue specimens will be performed using a 3-stage approach for efficient mutation detection: (1) allele-specific nucleotide (ASOs); (2) RNAse mismatch; and (3) PCR-based sequencing. This approach has already been operationalized in our laboratories. The investigators state that this study will provide comprehensive information in an epidemiologic context on the contribution of BRCA1 to the etiology of breast and ovarian cancers, and it will guide development of accurate counseling and intervention strategies for women who carry high-risk BRCA1 alleles.
| Bernstein, Jonine L; Lapinski, Robert; Lynch, Charles et al. (2002) Factors influencing mortality among young women with second primary breast carcinoma. Cancer 95:2051-8 |
